1. Field of the Invention
This invention relates to media for separating plasma or serum from whole blood.
Medical diagnostic assays are routinely performed on blood samples to determine the clinical status of patients by chemically detecting the presence and concentration of dissolved blood components, commonly referred to as analytes. Many of these assays are performed on a solid support such as a membrane or fibrous medium, with a color change occurring in relation to the concentration of the analyte being assayed. This color is then read visually or photometrically.
When using whole blood, the colored constituents of blood, viz, the erythrocytes, commonly known as red blood cells, can interfere with interpretation of the assay. For this reason, and as is well-known, the erythrocytes must be removed from the whole blood prior to the assay being performed on the remaining fluid. One known way of separating erythrocytes from plasma or serum is through centrifugation. However, this procedure entails an added, time-consuming step which is incompatible with situations requiring rapid diagnosis. In such cases the physician requires a system where a small amount of blood drawn from the patient can be assayed without having to centrifuge the sample. Specifically, it is desirable that erythrocytes can be quickly separated from blood such as is drawn from a fingerstick, thus leaving the lightly colored plasma to be available for subsequent assay.
In addition to separating erythrocytes from whole blood, the separation process must not cause hemolysis, i.e., rupture, of the erythrocytes during separation; otherwise, erythrocyte fragments could interfere with accurate measurement. Also, the components of the plasma or serum, such as proteins and lipids, must not be denatured by, nor undergo binding with, the separation medium. Finally, the separated fluid must be transported beyond the point of separation so that a sufficient quantity will be available for subsequent assay.
2. Description of the Prior Art
Several approaches to the problem of performing rapid diagnostic assays other than centrifugation have been developed. In one approach, such as is disclosed in U.S. Pat. No. 4,256,693 to Kondo et al. and U.S. Pat. No. 4,810,394 to Masuda, whole blood is allowed to migrate through successive layers of different materials where each layer performs separate and distinct functions. In another approach, as disclosed in U.S. Pat. Nos. 4,477,575 and 4,816,224 to Vogel et al., a separation layer consisting of glass microfibers having a bulk density of 0.1 to 0.5 g/cm.sup.3 has been used to separate erythrocytes from whole blood.
There are several known problems associated with these two approaches. First, manufacturing of multilayer separation media is expensive and difficult in comparison to manufacture of single-layer media which can perform the same or equivalent diagnostic functions. Secondly, papers or packings consisting entirely of glass microfibers are inherently weak and require great care in handling relative to multilayer media, membranes and other fibrous media typically used in diagnostic procedures. This characteristic, often referred to as fragility, is particularly serious in high volume diagnostic facilities where automated handling of materials is required. Although it is known that the strength of glass microfiber papers can be increased by adding binders which traditionally have been latex-based binders, such as polyvinyl acetate (PVA) or acrylics, these materials, or substances associated with their use, such as surfactants, are known to cause chemical interference with assays of the type contemplated in the present invention. Moreover, no specific composite media including such materials are known which can separate erythrocytes from whole blood without causing chemical interference.